Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica
The aim of this thesis was to understand more precisely the structural and environmental parameters governing the enantioselectivity of lipase B from Candida antarctica (CALB), involved in the discrimination of chiral secondary alcohols enantiomers. These compounds are used in particular for the syn...
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Online Access: | https://theses.hal.science/tel-00541104 https://theses.hal.science/tel-00541104/document https://theses.hal.science/tel-00541104/file/these_ZsMarton_v3.pdf |
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ftunivnantes:oai:HAL:tel-00541104v1 2023-05-15T14:00:09+02:00 Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica Modélisation moléculaire et expérimentation en réacteur solide/gaz pour la compréhension de la sélectivité de la lipase B de Candida antarctica Marton, Zsuzsanna LIttoral ENvironnement et Sociétés (LIENSs) La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS) Université de La Rochelle Marianne Graber 2010-07-22 https://theses.hal.science/tel-00541104 https://theses.hal.science/tel-00541104/document https://theses.hal.science/tel-00541104/file/these_ZsMarton_v3.pdf fr fre HAL CCSD NNT: 2010LAROS298 tel-00541104 https://theses.hal.science/tel-00541104 https://theses.hal.science/tel-00541104/document https://theses.hal.science/tel-00541104/file/these_ZsMarton_v3.pdf info:eu-repo/semantics/OpenAccess https://theses.hal.science/tel-00541104 Sciences agricoles. Université de La Rochelle, 2010. Français. ⟨NNT : 2010LAROS298⟩ Candida antarctica lipase B Enantioselectivity Solid/gas reactor Molecular modeling Inverse gas chromatography Alcoholysis Thermodynamic activity Lipase B de Candida antarctica Énantiosélectivité Réacteur solide/gaz Modélisation moléculaire Chromatographie gazeuse en phase inverse Alcoolyse Activité thermodynamique [SDV.SA]Life Sciences [q-bio]/Agricultural sciences info:eu-repo/semantics/doctoralThesis Theses 2010 ftunivnantes 2023-03-08T00:24:04Z The aim of this thesis was to understand more precisely the structural and environmental parameters governing the enantioselectivity of lipase B from Candida antarctica (CALB), involved in the discrimination of chiral secondary alcohols enantiomers. These compounds are used in particular for the synthesis of enantiomerically pure pharmaceutical molecules. Initially a systematic study of the orientation of butan-2-ol and pentan-2-ol in the active site was performed by molecular modeling. The results suggest the existence of additional binding modes to those mentioned in the literature. The potential energy comparison of the most stable conformations of the substrate, combined with the existence of non productive binding modes, allowed us to explain qualitatively the enantiopreference of CALB for the R form. Using the solid/gas reactor, we have shown that hydrophobic residues forming the access channel of substrate to the active site (Ile189, Leu278 and Ala282), played a significant role in the enantioselectivity of CALB towards secondary alcohols. The influence of the alkoxy part of the acyl donor on the enatiomeric ratio E has also been highlighted. Furthermore, we showed that isosteric mutations of the stereoselective pocket led to changes in pentan-2-ol activation thermodynamic parameters of acylation, probably due to changes in the hydrogen bonds network formed between residues of the pocket. Studies of water and substrates adsorption on the immobilized enzyme allowed us to relate the hydration status of CALB with specific effects of water on the enzyme activity and selectivity. L’objectif de cette thèse était de mieux comprendre les paramètres structuraux et environnementaux gouvernant l’énantiosélectivité de la lipase B de Candida antarctica (CALB), lors de la résolution des alcools secondaires linéaires chiraux. Ces composés sont notamment utilisés comme synthons chiraux dans l’industrie pharmaceutique. Dans un premier temps, une étude systématique des orientations du butan-2-ol et du pentan-2-ol au sein ... Doctoral or Postdoctoral Thesis Antarc* Antarctica Université de Nantes: HAL-UNIV-NANTES |
institution |
Open Polar |
collection |
Université de Nantes: HAL-UNIV-NANTES |
op_collection_id |
ftunivnantes |
language |
French |
topic |
Candida antarctica lipase B Enantioselectivity Solid/gas reactor Molecular modeling Inverse gas chromatography Alcoholysis Thermodynamic activity Lipase B de Candida antarctica Énantiosélectivité Réacteur solide/gaz Modélisation moléculaire Chromatographie gazeuse en phase inverse Alcoolyse Activité thermodynamique [SDV.SA]Life Sciences [q-bio]/Agricultural sciences |
spellingShingle |
Candida antarctica lipase B Enantioselectivity Solid/gas reactor Molecular modeling Inverse gas chromatography Alcoholysis Thermodynamic activity Lipase B de Candida antarctica Énantiosélectivité Réacteur solide/gaz Modélisation moléculaire Chromatographie gazeuse en phase inverse Alcoolyse Activité thermodynamique [SDV.SA]Life Sciences [q-bio]/Agricultural sciences Marton, Zsuzsanna Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica |
topic_facet |
Candida antarctica lipase B Enantioselectivity Solid/gas reactor Molecular modeling Inverse gas chromatography Alcoholysis Thermodynamic activity Lipase B de Candida antarctica Énantiosélectivité Réacteur solide/gaz Modélisation moléculaire Chromatographie gazeuse en phase inverse Alcoolyse Activité thermodynamique [SDV.SA]Life Sciences [q-bio]/Agricultural sciences |
description |
The aim of this thesis was to understand more precisely the structural and environmental parameters governing the enantioselectivity of lipase B from Candida antarctica (CALB), involved in the discrimination of chiral secondary alcohols enantiomers. These compounds are used in particular for the synthesis of enantiomerically pure pharmaceutical molecules. Initially a systematic study of the orientation of butan-2-ol and pentan-2-ol in the active site was performed by molecular modeling. The results suggest the existence of additional binding modes to those mentioned in the literature. The potential energy comparison of the most stable conformations of the substrate, combined with the existence of non productive binding modes, allowed us to explain qualitatively the enantiopreference of CALB for the R form. Using the solid/gas reactor, we have shown that hydrophobic residues forming the access channel of substrate to the active site (Ile189, Leu278 and Ala282), played a significant role in the enantioselectivity of CALB towards secondary alcohols. The influence of the alkoxy part of the acyl donor on the enatiomeric ratio E has also been highlighted. Furthermore, we showed that isosteric mutations of the stereoselective pocket led to changes in pentan-2-ol activation thermodynamic parameters of acylation, probably due to changes in the hydrogen bonds network formed between residues of the pocket. Studies of water and substrates adsorption on the immobilized enzyme allowed us to relate the hydration status of CALB with specific effects of water on the enzyme activity and selectivity. L’objectif de cette thèse était de mieux comprendre les paramètres structuraux et environnementaux gouvernant l’énantiosélectivité de la lipase B de Candida antarctica (CALB), lors de la résolution des alcools secondaires linéaires chiraux. Ces composés sont notamment utilisés comme synthons chiraux dans l’industrie pharmaceutique. Dans un premier temps, une étude systématique des orientations du butan-2-ol et du pentan-2-ol au sein ... |
author2 |
LIttoral ENvironnement et Sociétés (LIENSs) La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS) Université de La Rochelle Marianne Graber |
format |
Doctoral or Postdoctoral Thesis |
author |
Marton, Zsuzsanna |
author_facet |
Marton, Zsuzsanna |
author_sort |
Marton, Zsuzsanna |
title |
Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica |
title_short |
Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica |
title_full |
Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica |
title_fullStr |
Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica |
title_full_unstemmed |
Molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase B from Candida antarctica |
title_sort |
molecular modeling and experimentation in solid/gas reactor for understanding the selectivity of lipase b from candida antarctica |
publisher |
HAL CCSD |
publishDate |
2010 |
url |
https://theses.hal.science/tel-00541104 https://theses.hal.science/tel-00541104/document https://theses.hal.science/tel-00541104/file/these_ZsMarton_v3.pdf |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
https://theses.hal.science/tel-00541104 Sciences agricoles. Université de La Rochelle, 2010. Français. ⟨NNT : 2010LAROS298⟩ |
op_relation |
NNT: 2010LAROS298 tel-00541104 https://theses.hal.science/tel-00541104 https://theses.hal.science/tel-00541104/document https://theses.hal.science/tel-00541104/file/these_ZsMarton_v3.pdf |
op_rights |
info:eu-repo/semantics/OpenAccess |
_version_ |
1766269146147848192 |